Taxus Baccata

by | Mar 15, 2018 | Taxus Baccata

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22q13 Deletion Syndrome (spoken as twenty two q one three), also known as Phelan-McDermid Syndrome, is a genetic disorder caused by deletions or rearrangements on chromosome 22. The deletion occurs at the terminal end of the chromosome at the location designated q13.3. Some terminal deletions can be uncovered by karyotype analysis, but many deletions are too small (microdeletions). The availability of DNA microarraytechnology, and microarray's utility in looking for multiple genetic problems simultaneously, have made this technology the diagnostic tool of choice. However, fluorescence in situ hybridization (FISH) tests are valuable for diagnosing cases of mosaicism (mosaic genetics) and chromosomal rearrangements (e.g., ring chromosome, unbalanced chromosomal translocation). There is a great deal of interest in one gene that is often deleted in Phelan-McDermid Syndrome, SHANK3 (also known as PROSAP2). Errors in this gene have been associated with Autism Spectrum Disorder (ASD) and Schizophrenia [1]. However, it is difficult to interpret the importance of one gene in these disorders, since individuals with these disorders tend to have more rare genetic mutations than the general population [2].

Phelan-McDermid Syndrome is characterized by global developmental delay, absent or severely delayed speech, and neonatal hypotonia [3]. There are approximately 600 reported cases of Phelan-McDermid Syndrome worldwide.

Characteristics

The core characteristics of 22q13 Deletion Syndrome (listed above) have a major impact on the individual. However, in addition to these characteristics, there are other manifestations than may range from mild to severe:

Physical

  • Absent to severely delayed speech: 99%
  • Hypotonia (poor muscle tone): 97%
  • Normal to accelerated growth: 95%
  • Increased tolerance to pain: 86%
  • Thin, flaky toenails: 78%
  • Large, fleshy hands: 68%
  • Prominent, poorly formed ears: 65%
  • Pointed chin: 62%
  • Dolichocephaly (elongated head): 57%
  • Ptosis (eyelid) (droopy eyelids): 57%
  • Poor thermoregulation: 51%

Behavioral

  • Chewing on non food items (clothing, bedding, toys):70%
  • Teeth grinding: (percent undetermined)
  • Autistic behaviors: (percent undetermined)
  • Tongue thrusting: (percent undetermined)
  • Hair pulling: (percent undetermined)
  • Aversion to clothes: (percent undetermined)

Etiology

The deletion affects the terminal region of the long arm of chromosome 22 (the paternal chromosome in 75% of cases), from 22q13.3 to 22qter. Although the deletion is most typically a result of a de novo mutation, there is an inherited form resulting from familial chromosomal translocations involving the 22 chromosome. In the de novo form, the size of the deletion is variable and can go from 130kbp (130,000 base pairs) to 9Mbp (9,000,000 base pairs). At one time it was thought that deletion size was not related to the core clinical features [4]. That observation lead to great emphasis on the SHANK3 gene. More recent studies with larger cohorts, however, have demonstrate that the core features do depend upon deletion size [5]. There remains a great deal of interest in the SHANK3 gene, as well as growing interest in the MAPK8IP2 (also called IB2) and PLXNB2 genes[6] [7].


Incidence

The incidence of the 22q13 deletion syndrome is uncertain. Current thinking is that 22q13 deletion syndrome remains largely under-diagnosed, and may be one of the principal causes of idiopathic mental retardation.

See also

Notes

  1. ^ Gauthier; et al. (2010). "De novo mutations in the gene encoding the synaptic scaffolding protein SHANK3 in patients ascertained for schizophrenia". Proc Natl Acad Sci. 107 (17): 7863–8. doi:10.1073/pnas.0906232107. PMID 20385823. {{cite journal}}: Explicit use of et al. in: |author= (help)
  2. ^ Stankiewicz P, Lupski JR (2010). "Structural variation in the human genome and its role in disease". Annu Rev Med. 61: 437–55. PMID 10.1146/annurev-med-100708-204735. {{cite journal}}: Check |pmid= value (help)
  3. ^ Phelan MC, McDermid HE (2011). "The 22q13.3 Deletion Syndrome (Phelan-McDermid Syndrome)". Mol Syndromol. 2 (1): 186–201. doi:10.1159/000334260. PMID 22670140.
  4. ^ Wilson HL, Wong AC, Shaw SR; et al. (2003). "Molecular characterisation of the 22q13 deletion syndrome supports the role of haploinsufficiency of SHANK3/PROSAP2 in the major neurological symptoms". J. Med. Genet. 40 (8): 575–84. doi:10.1136/jmg.40.8.575. PMC 1735560. PMID 12920066. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
  5. ^ Sarasua SM; et al. (2011). "Association between deletion size and important phenotypes expands the genomic region of interest in Phelan-McDermid syndrome (22q13 deletion syndrome)". J Med Genet. 48 (11): 761–6. doi:10.1136/jmedgenet-2011-100225. PMID 21984749. {{cite journal}}: Explicit use of et al. in: |author= (help)
  6. ^ Giza J; et al. (2010). "Behavioral and cerebellar transmission deficits in mice lacking the autism-linked gene islet brain-2". J Neurosci. 30 (44): 14805–16. doi:10.1523/JNEUROSCI.1161-10.2010.. PMID 12920066. {{cite journal}}: Check |doi= value (help); Explicit use of et al. in: |author= (help)
  7. ^ Aldinger KA; et al. (2013). "Cerebellar and posterior fossa malformations in patients with autism-associated chromosome 22q13 terminal deletion". Am J Med Genet A. 161 (1): 131–6. doi:10.1002/ajmg.a.35700.. PMID 23225497. {{cite journal}}: Check |doi= value (help); Explicit use of et al. in: |author= (help)

References

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